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Background: This study evaluated the distribution of epidermal growth factor receptor (EGFR) T790M mutations in treatment-naïve tumor and normal samples obtained from cancer patients. Methods: We utilized allele-specific PCR (AS-PCR), digital droplet PCR (ddPCR) and next generation sequencing (NGS) to detect EGFR T790M allele in several collections of tumor and normal human tissues. Results: AS-PCR analysis of treatment-naïve tumor samples revealed somatic T790M mutation in 3/394 (1%) non-small cell lung carcinomas (NSCLC) carrying the tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutation, but in none of 334 NSCLC lacking EGFR exon 19 deletions (ex19del) or L858R substitutions and in none of 235 non-lung tumors. Use of highly sensitive and quantitative assays, such as ddPCR and NGS, produced a high number of T790M-specific signals even in presumably T790M-negative DNA specimens. This background noise was evidently higher in degraded DNA isolated from formalin-fixed paraffin-embedded tissues as compared to high molecular weight DNA. A combination of AS-PCR, ddPCR and NGS revealed mosaic EGFR T790M allele in 2/68 (3%) NSCLC treated with the first-generation TKI. Both these tumors produced evident and durable response to gefitinib. Conclusion: Detection of mosaic EGFR T790M mutation in treatment-naïve samples may be compromised by yet unresolved technical issues and may have limited clinical value.

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Thin-walled shell-type structures are widely used in various branches of technology and industry. Such structures under operating conditions are usually exposed to various loads, including thermomechanical ones. Real shell structures, as a rule, have a complex shapes. To increase reliability, reduce material consumption, for technological reasons, they are designed as inhomogeneous systems in thickness. This causes a great and constant interest of engineers and designers in the problems of investigating the behavior of elastic thin-walled shell structures. The work is devoted to the method of analysis of geometrically nonlinear deformation, stability, post-buckling behavior and natural vibrations of thin elastic shells of complex shape and structure under the action of static thermomechanical loads. The unified design model has been created on the basis of the developed universal spatial finite element with introduced additional variable parameters. The model takes into account the multilayer material structure and geometric features for structural elements of the thin shell. The shells can be reinforced with ribs and cover plates, weakened by cavities, channels and holes, have sharp bends in the mid-surface. Such a uniform formulation made it possible to create a unified finite element model of the shells with an inhomogeneous structure. It is shown on a number of problems that the method presented in this article is an effective tool for analyzing geometrically nonlinear deformation, stability, post-buckling behavior and natural vibrations of thin elastic shells of an inhomogeneous structure under the action of static thermomechanical loads.